Evaluation of the Efficacy and Safety of DA-9601 versus Its New Formulation, DA-5204, in Patients with Gastritis: Phase III, Randomized, Double-Blind, Non-Inferiority Study

This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was −0.4% (95% confidence interval, −9.8% to 9.1%), which was above the non-inferiority margin of −14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670)

Benzoxazole Derivative B-98 Ameliorates Dextran Sulfate Sodium-induced Acute Murine Colitis and the Change of T Cell Profiles in Acute Murine Colitis Model / 대한소화기학회지

BACKGROUND/AIMS: The unique role of enzyme 5-lipoxygenase (5-LO) in the production of leukotrienes makes it a therapeutic target for inflammatory bowel disease (IBD). The aim of this study was to evaluate the effects of B-98, a newly synthesized benzoxazole derivatives and a novel 5-LO inhibitor, in a mouse model of IBD induced by dextran sulfate sodium (DSS). METHODS: C57BL/6 mice were randomly assigned to four groups: normal control, DSS colitis (DSS+saline), low dose B-98 (DSS+B-98 20 mg/kg) and high dose B-98 (DSS+B-98 100 mg/kg). B-98 was administered with 3% DSS intraperitoneally. The severity of the colitis was assessed via the disease activity index (DAI), colon length, and histopathologic grading. The production of inflammatory cytokines interleukin (IL)-6 was determined by RT-PCR. Th cells were examined for the proportion of Th1 cell, Th2 cell, Th9 cell, Th17 cell and Treg cell using intracellular cytometry. RESULTS: The B-98 group showed lower DAI, less shortening of the colon length and lower histopathologic grading compared with the DSS colitis group (p<0.01). The expression of IL-6 in colonic tissue was significantly lower in the B-98 groups than the DSS colitis group (p<0.05). The cellular profiles revealed that the Th1, Th9 and Th17 cells were increased in the DSS colitis group compared to the B-98 group (p<0.05). CONCLUSIONS: Our results suggest that acute intestinal inflammation is reduced in the group treated with B-98 by Th1, Th9 and Th17 involved cellular immunity.

Meta-analysis: the Effect of Lactobacillus Supplementation on Helicobacter pylori Eradication Rates and Side Effects during Treatment

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) is causally associated with gastritis and peptic ulcer diseases. Recent data have demonstrated that triple therapy with amoxicillin, clarithromycin, and a proton pump inhibitor has an eradication rate of only 74~76% and new therapeutic protocols may be necessary. The aim of this study was to investigate the effects of Lactobacillus as supplementation to anti-H. pylori regimens on H. pylori eradication rates and therapy-associated side effects. MATERIALS AND METHODS: The PubMed, Medline and Korean Medical Database were searched in January 2012, with no language restrictions, for randomized controlled trials; additional references were obtained from reviewed articles. We included trials comparing Lactobacillus supplementation to placebo or no treatment during anti-H. pylori regimens. Meta-analysis was performed with Review Manager. RESULTS: Eleven trials involving a total of 1,107 participants met the inclusion criteria. Compared with placebo or no intervention, Lactobacillus given along with anti-H. pylori regimens significantly increased the eradication rate [84.7% vs. 78.8%, odds ratio (OR) 1.75, 95% confidence interval (CI) 1.26~2.42] and reduced the risk of overall H. pylori therapy related adverse effects (35.4% vs. 48.6%, OR 0.56, 95% CI 0.38~0.81), particularly of diarrhea (7.5% vs. 20.6%, OR 0.31, 95% CI 0.18~0.54), bloating (19.2% vs. 29.9%, OR 0.53, 95% CI 0.32~0.88) and taste disturbance (17.6% vs. 34.8%, OR 0.37, 95% CI 0.21~0.64). There were no significant differences between groups in the risk of other adverse effects. CONCLUSIONS: Our review suggests that supplementation with Lactobacilli could be effective in increasing eradication rates of anti-H. pylori therapy. Furthermore, Lactobacilli showed a positive impact on some H. pylori therapy-related side effects, particularly diarrhea, bloating and taste disturbance.

Analysis of Risk Factors for Low Bone Mineral Density in Patients with Inflammatory Bowel Disease / 대한소화기학회지

BACKGROUND/AIMS: Several clinical risk factors for low bone mineral density (BMD) in the patients with inflammatory bowel disease (IBD) have been suggested. However, its prevalence and pathophysiology in Korean population have not been fully studied. The aim of this study was to investigate the prevalence and risk factors for low BMD in Korean IBD patient. METHODS: BMD of the lumbar spine and femur was evaluated using dual-energy X-ray absorptiometry in 30 patients with IBD. Biochemical parameters of bone metabolism, such as serum calcium, phosphorus, osteocalcin, and deoxypyridinoline were measured. The associations between low BMD and clinical parameters such as disease duration, disease activity, drug history, body mass index (BMI), and others were evaluated retrospectively using medical records. RESULTS: Low BMD at the lumbar spine or femur was observed in 63.3% of the patients, and there was no significant difference between the patients with Crohn's disease and ulcerative colitis. Clinical and biochemical parameters were irrelevant to BMD. In the patients without glucocorticoid treatment prior to BMD measurement, already 50.0% of patients had low BMD. CONCLUSIONS: Low BMD is a common feature in Korean IBD patients, even those who do not use glucocorticoid. The multiple factors may be involved in the pathogenesis of low BMD. Therefore, BMD should be examined in all IBD patients, irrespective of glucocorticoid treatment.

A Case of Ischemic Colitis Associated with the Herbal Food Supplement Ma Huang

Ischemic colitis is a condition that usually occurs in the elderly, as a form of vascular disease. However, ischemic colitis also occurs, though rarely, in healthy young adults. Moreover, food supplements containing Ephedra sinica or ma huang have been linked to adverse central nervous and cardiovascular events. A 40-year-old man was admitted to our emergency department after 2 episodes of abdominal pain and bloody diarrhea that lasted 24 hours. His medical history was unremarkable for risk factors of bowel ischemia, except for well-controlled hypertension. However, a weight-loss supplement, Ephedra sinica, had been prescribed for daily use during the previous month. Both abdominal/pelvic computed tomography and colonoscopy revealed findings compatible with ischemic colitis. His conditions spontaneously improved without any serious complications, and he was advised to discontinue the use of herbal medications containing ephedrine. In this paper, we describe a case of ischemic colitis that was potentially linked to the use of ma huang with a review of the relevant literature.

A Case of Ischemic Colitis in a Young Woman with Chronic Obstructive Type Constipation / 대한소화관운동학회지

Although ischemic colitis is often considered to be a condition occurred in elderly patients or in patients with vascular diseases, it also can occur in younger healthy persons. Some drugs, such as oral contraceptives, may play an important role in the development of ischemic colitis in young women. However, constipation also can play an important role in this condition. We recently experienced a case of reversible ischemic colitis of a young woman, who had been suffered from obstructive type of chronic constipation, after taking a laxative and enema. We report this case with literature review. Proper managements and educations in patients with chronic constipation should be emphasized.

A Prospective Endoscopic Blind Trial Comparing Precolonoscopy Bowel Cleansing Methods / 대한소화기내시경학회지

BACKGROUND AND AIMS: Although some authors have suggested that sodium phosphate (NaP) is more effective than polyethylene glycol (PEG) in bowel cleansing, there has been no crossover study proving the superiority of NaP over PEG in bowel cleansing and patients' compliance. The aim of this study was to compare the two solutions for colonoscopy, PEG and NaP, through crossover design with regard to patients' compliance, cleansing ability and side effects. METHODS: Thirty patients underwent two separate colonoscopies for colonic polyp(s) with PEG and NaP, respectively. Before and after bowel preparation, blood pressure, body weight, and serum biochemical parameters were measured in all patients. In addition, a detailed questionnaire was used to assess side effects and the patients' preference. The presence of bubbles, types of residual stool, and overall quality of colon cleansing were assessed by one endoscopist blinded to the type of preparation used. In each colonoscopy, two biopsy specimens were taken at rectum. RESULTS: In the NaP group, but not in the PEG group, there were significant changes in several biochemical parameters including sodium ( +3.0 +/- 3.0 mEq/L), potassium ( -0.3 +/- 0.3mEq/L), calcium ( -0.5 +/- 0.5 mg/dL), phosphorus ( +3.9 +/- 2.2 mg/dL) and osmolarity ( +10.1 +/- 9.3 mOsm/kg) after bowel preparation. In addition, the degree of body weight change was greater with NaP ( -2.2 +/- 2.3 kg) than with PEG ( -1.2 +/- 2.0 kg) (p=0.06) and the formation of bubbles that disturb luminal observation was more frequently found in the NaP group (p<0.01). There was no difference, however, in the type of residual stool and the overall quality of bowel preparation between the two groups and no significant mucosal change was noted after bowel preparation in both groups. Moreover, PEG was found to be more difficult to take than NaP (p<0.05) and among the 30 patients, 26 (87%) preferred NaP, while only two favored PEG (p<0.01). CONCLUSIONS: We conclude that NaP can replace PEG at least in patients with good general condition. Further studies to decrease the incidence of bubbles and to establish subgroups suitable for NaP are needed.